Dinitrimines

ABSTRACT

Lower aliphatic dinitrimines are disclosed, including both open chain and cyclic dinitrimines. They are prepared by the reaction of a dioxime with dinitrogen tetroxide at low temperatures. The IR spectrum is compared with that of the known compound, camphor nitrimine and ultraviolet measurement indicate spectra typical of nitrimines. The compounds have uses in pharmocology, in tobacco, as blowing agents and as propellants.

States Patent 91 eardeleben, Jr. 51 Jan. 9, 1973 DIINHTRIMINES 75] Inventor: John F. DeBard elebem jrl, Rich- PrimaryEMmi'Ier-Le0nZ1tver v mend Va Assistant Examiner-Gerald A. Schwartz a Att0meyWatson, Leavenworth & Kelton [73] Asslgnee: Philip Morris Incorporated, New

57 ABSTRACT [22] Flled: June 1970 Lower aliphatic dinitrimines are disclosed, including [21] Appl.No.: 42,586 both open chain and cyclic dinitrimines. They are prepared by the reaction of a dioxime with dinitrogen [52] us'm 260/566! 149/92 260/25 R tetroxide at low temperatures. The IR spectrum is 6 compared with that of the known compound, camphor 51 Int. Cl ..C07c 119/00 nimmine and ultravidet measurement indicate P [58] Field of Search ..260/566 R yp of nitrimines- The compounds have uses in pharmocology, in tobacco, as blowing agents and as References Cited propellants.

OTHER PUBLICATIONS Chemical Abstracts, Vol. 41, column 5506 (1947) 8 Claims, N0 Drawings DINITRIMINES This invention relates to new and useful nitrimine compounds and more particularly relates to useful dinitrimines and a method for producing them.

The compounds known as nitrimines are also known as nitroimines or by the earlier term of pernitroso compounds. The latter term was based on the belief that the structure of the compounds should be indicated by a configuration such as However, J. P. Freeman, J. Org. Chem. 26, 4190-4193 (1961) supplies support for a nitrimine structure indicated, for example, as R C=NNO On the basis of the Freeman publication the com pounds of the invention are considered to be dinitrimines and thus fall within the scope of the following illustrative structural formulas:

in which R and R may be similar or different and represent either hydrogen or a lower alkyl preferably of one to six carbon atoms while R is either hydrogen or a lower alkyl of one to two carbon atoms while m and m are similar or dissimilar integers representing 0, l or 2, with n standing for the integer 0, l, 2 or 3 and is only when R is a lower alkyl.

The compounds of the invention have been found useful as blowing agents for foaming of polymers, for example, high density polyethylenes. Such foamed polymers would find useful application in bedding, packaging material, etc. The compounds are also useful as propellants. When brought above a critical temperature, from about 135C. to about 200C., decomposition products are formed among which are acetone, branched-chain nitriles and gaseous products, the latter being largely NO and N0 It has also been found that the cyclohexanedinitrimines have substantial anti-viral activity when submitted to pharmacological examination under standard testing procedures. In such a test, mice are inoculated with the virus herpes simplex. The compound to.

be treated is administered subcutaneously and the number of survivors and survival time in each group (varying dosage as well as 0 dose control) are noted. Dosages of test compound were 40 and 400 pg, as well as 4 mg. and the activity of these dosages compared with controls. With the cyclohexane-dinitrimines antiviral activity was noted not only at the microgram amounts indicated but at the dosage of 4 mg. without causing toxic manifestations. Such compounds would therefore have value in experimental or comparative pharmacology for anti-viral studies.

The process for the preparation of the compounds of the invention may be illustrated by the following reaction scheme, the various symbols being the same as previously mentioned:

Cyclic compounds of the type shown in formula I are prepared by means known to the art. Thus, with respect to compounds of formula I, a selected afi-unsaturated ketone may be reacted with dialkylmalonate, followed by hydrolysis, to a cyclic 1,3-diketo compound unsubstituted in the 2-position as essentially described in Org. Syn. Coll. Vol. 11, 200 (1943). Alkylation at the 2- position may be carried out using a lower alkyl halide, for example, methyl bromide. The 1,3-dioxime is formed by reaction with hydroxylamine in an aqueous or alcoholic medium, following known procedures. With respect to non-cyclic aliphatic compounds of type 11, one merely reacts the selected di-ketone with hydroxylamine as indicated.

In the preparation of the desired compounds III or IV, as will be noted above, the selected dioxime is dissolved in an inert solvent, such as dlialkyl ethers, benzenoid or chlorinated solvents but preferably diethyl ether. The reaction may be carried out from 20 to C., but preferably in the range of 0 to 10C. Dinitrogen tetroxide in the same solvent is added dropwise to the extent of at least 2 mols per mol of dioxime with stirring and cooling if necessary to keep the reac tants within the indicated temperature range. After the reaction is complete, the reactant mixture is concentrated, and the dinitrimine usually precipitates out of solution. Purification is carried out by conventional procedures to obtain a substantially pure, usually crystalline product.

The following examples are provided for greater detail and are illustrative of the best mode for carrying out the invention.

EXAMPLE 1 2,2-Dimethyll ,3dinitriminocyclohexane A solution of 6.0 g. (0.035 mole) of 2,2-dimethylcyclohexane-l,3-dione dioxime in 300 ml. of absolute ethyl ether under nitrogen was cooled to 0C. in an icesalt bath. A cold solution of 6.6 g. (0.071 mole) of N 0,, in ml. of ether was addedl dropwise with stirring over 30 minutes while maintaining the reaction mixture at 0 to 5C. The clear solution turned green, and a white solid began to crystallize out. Stirring was continued for 1 hour while allowing; the temperature to slowly rise. The solid was filtered and washed with ether yielding 3.0 g. of material, m.p. l47-148 dec. Concentration of the ether solution of one-half its original volume gave an additional 0.8 g. of material with the same meltingpoint. Recrystallization from a mixture of n-hexane/ether gave an analytical sample with melting point 149-150C. dec.* (*The melting point is variable depending on the rate of heating.) U1- traviolet A 95% 265 mg. is typical of nitrimines. The IR spectrum compared with that of camphor nitrimine. There is a medium band at 1610 and a weak band at 1627 cm (C= N), a strong band at 1567 cm (N asym.), a strong band at 1316 cm'(N0 sym.), medium bands at 885 cm (N-N) and 810 cm" (N- 0). NMR in CDCl:, shows a singlet at 81.55, a multiplet at 2.0, and a multiplet at 2.75 integrating respectively for 6, 2 and 4 protons. These protons are identified, respectively, as those on the methyls, the -methylene, and the 4,6-methylene carbons. Anal. Calcd. for C H NO 3 C, 42.10; H, 5.30: N, 24.55. Found: C, 42.06; H, 5.49; N, 24.27.

EXAMPLE 2 1,3-Dinitrimino-2,2,5,5-tetramethylcyclohexane A solution of 19.8 g. (0.1 mole) of 2,2,5,5- tetramethylcyclohexane-l,3-dione dioxime in 500 ml. of absolute ether under nitrogen-was cooled to 5C. in an icebath. A cold solution of 32.2 g. (0.35 mole) of N 0, in 150 ml. of ether was added dropwise with stirring while maintaining the temperature at 5 to C. Stirring was continued for 4 hours at 5 to 10C. and the reaction mixture then allowed to come to room temperature and stirred overnight. Most of the ether was removed with a stream of nitrogen and a solid crystallized out. This solid was removed by filtration and washed with n-hexane. The filtrate yielded a second crop of material. This was collected and combined with the original crystals. The total crude material was crystallized from 10/] n-hexane/ether to give 17.1 g. (68 percent yield) of material with melting point l69l70 dec.* (*The melting point is variable depending on the rate of heating.) Ultraviolet k '265 mg. is typical of nitrimines. The IR spectrum had peaks as follows: medium at 1608 and weak at 1628 cm",(C=N), strong at 1567 and 1558 cm" (NO,

asym. strong at 1316 cm (NO: sym.), and medium at 885 cm (N-N) and at 810 cm N-O). NMR ind acetone showed singlets at 81.05, 1.55, and 2.7 integrating respectively for 6,6 and 4 protons. These are identified, respectively, as the protons on the 5,5- methyls, the 2,2-methyls, and the 4,6-methylene car- I bons. Anal. Calcd. for C H N 0 C, 46.87; H, 6.29;

N, 21.86. Found; C, 47.05; H, 6.48; N, 21.37.

When submitted to pharmacological evaluation the compound was found active against herpes simplex in standard test animals.

EXAMPLE 3 reaction mixture was allowed to come to room temperature and stirred overnight. The volume of solvent was reduc'ed'to 250 ml. by passing nitrogen over the solution. A white solid came out which was filtered and washed with n-hexane to give a crude material with melting point l30-135C.' Three recrystallizations from n-heptane gave an analytical sample with melting point l34.5135 dec.* (*The melting point isvariable depending on the rate of heating.)

Ultraviolet spectrum shows only end absorption. Very probably both syn and anti forms of the dinitrimine were produced. The form finally isolated in pure form is believed to be the anti form on the basis of the NMR spectrum and the absence of a UV peak, suggesting cancellation by opposed nitrimine groups. NMR in d -benzene shows a single peak at 81.1 corresponding to the equivalent methyl protons. 1n the syn form half the methyl protons would be deshielded by the nitro groups as compared with the other half, and two peaks would be expected. The spectrum of IR absorption had bands as follows: medium at 1660 cm" (C=N), strong at 1586 cm (N0 asym.), strong at 1310 cm (N0 sym.), and medium at 888 cm (N- N) and 753 cm" (NO). Anal. calcd. for c,,H,,N,o,; C, 42.10; H, 5.30; N, 24.55. Found: C, 41.74; H, 5.28; N, 23.80.

Example 4 2,2-Diethyll ,3-dinitriminocyclooctane A solution of l 1.1 g. (0.05 mole) of 2,2-diethylcyclooctane-1,3-dione dioxime dissolved in 300 ml. of absolute ethyl ether under nitrogen is cooled to 0C. in an ice-salt bath. A cold solution of 9.2g. (0.1 mole) of N 0, in ml. of ether is added dropwise with stirring over one hour while the mixture is maintained at 0 to 5C. A solid begins to precipitate. Stirring is continued while the temperature is allowed to rise. The solid is removed by filtration and more solid is recovered by 'concentration of the solution to about one-half its volume. The product is recrystallized from n-hexane/ether and its identity as the dinitrimine is confirmed by analysis and absorption spectra as in preceding examples.

The treatment of the dioxime of 2-ethyl-2-methyl- EXAMPLE 5 3,3-Dimethyl-2,4-dinitriminopentane A solution of 15.8 g. (0.1 mole) of 3,3-dimethylpentane-2,4-dione dioxime in 500 ml. of absolute ethyl ether under nitrogen is cooled to 0C. in an ice-salt bath. A cold solution of 18.4 g. (0.2 mole) of N 0 in 200 ml. of ether is added dropwise with stirring while the temperature is maintained at 5 to 10"C. Stirring is continued for one hour, after which the mixture is alin which each R is independently selected from the group consisting of alkyls of one to six carbon atoms, and each R is independently selected from the group consisting of hydrogen and alkyls of one to six carbon atoms, while m and m are similar or dissimilar integers from O to 2; and each R is independently selected from the group consisting of hydrogen and lower alkyl of one to two carbon atoms, while n is an integer 0 to 3; with the proviso that R is alkyl when m and m are both 0 and R is a lower alkyl when n is 0.

2. The compound of claim 1, formula I, in which R is methyl and R is hydrogen.

3. The compound of claim 1, formula I, in which R and R are each methyl.

4. The compound of claim 1, formula I, in which m and m is 0.

5. The compound of claim 1, fiormula I, in which m and m is l.

6. The compound of claim 1, 2,2-dimethyl-l ,3- dinitriminocyclohexane.

7. The compound of claim 1, l,3-dinitrimino-2,2,5,5- tetramethylcyclohexane.

8. The compound of claim I, anti-1,3-dinitrimino- 2,2,4,4tetramethylcyclobutane.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 7 9.941 Dated January 9, 1973 Inventor(s) John F. De Bard'eleben It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, line 2 0, "formulas" should be formulae Column 'l,' in the figure designated "(II)" the portion of the structure indicated to be "(CH C should be v H v 9" C.- Column 3, line 13, "cm"" should be cm Column 3,' line 20, "C H N0 should be C H N O Column 4, line 41, "n-hex-" should be -hex- Claim 1, in the figure designated."(II)", the portionof the structure indicated to be '-(CH C should be Signed and sealed this 9th day of April 197A.

(SEAL) v Attest:

EDWARD I I.FLETGHER,JR; 1 C. MARSHALL DANN Atte sting Officer v 7 Commissionerof Patents UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent 3.709.941 Dated January 9, 1973 Inventofls) John F. De Bardeleben It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, line 2 0, "formulas" should be formulae Column 1, in the figure designated "(II)" the portion of the structure indicated to be "-(CH --'C should be.

-- -(CH c t- Column 3, line 13, "cm'" should be cm' Column 3, line 20, "C H NO4" should be C H N O Column 4, line 41, "nhex-" should be -hex- Claim 1, in the figure designated "(Il)", the portionof the structure indicated to be "'-(CH C should be e I -(cH c Signed and sealed this 9th day of April 197b,.

(SEAL) Attest:

EDWARD M.FLETCHER,JR; C MARSHALL DANN Attesting Officer Commissioner of Patents 

2. The compound of claim 1, formula I, in which R is methyl and R'' is hydrogen.
 3. The compound of claim 1, formula I, in which R and R'' are each methyl.
 4. The compound of claim 1, formula I, in which m and m'' is
 0. 5. The compound of claim 1, formula I, in which m and m'' is
 1. 6. The compound of claim 1, 2,2-dimethyl-1,3-dinitriminocyclohexane.
 7. The compound of claim 1, 1,3-dinitrimino-2,2,5,5-tetramethylcyclohexane.
 8. The compound of claim 1, anti-1,3-dinitrimino-2,2,4,4-tetramethylcyclobutane. 